Throughout this application various publications are referred to in parenthesis. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference in their entireties into the subject application to more fully describe the art to which the subject application pertains.
Melanin is a high molecular weight pigment that is ubiquitous in nature and has a variety of biological functions (5). Melanins are found in all biological kingdoms. These pigments are among the most stable, insoluble, and resistant of biological materials (6). Melanins can have different structures depending on the biosynthetic pathway and precursor molecules. Some definitions of melanin have focused on chemical and physical properties of melanins instead of defined structures (7). Melanins can be synthesized in the laboratory by chemical means or by many living organisms. Melanins formed by the oxidative polymerization of phenolic compounds are usually dark brown or black (6). However, melanins may have other colors as illustrated by the finding that dopamine-derived melanin is reddish-brown. Fungi can make melanins from at least two major biosynthetic pathways, employing the precursor 1,8-dihydroxynapthalene (DHN melanin) or the oxidation of suitable tyrosine derivatives like dihydroxyphenylalanine (DOPA-melanin) (6). The fungus C. neoformans can make melanins from a wide variety of phenolic compounds which are oxidized by a laccase enzyme (8-10). Many fungi constitutively synthesize melanin (11).
Every year 1.4 million people are diagnosed with cancer in the U.S. and half of them will undergo some form of radiation therapy in the course of their disease. The availability of radioprotective compounds would alleviate the morbidity associated with the radiation exposure. The doses received by millions of patients during diagnostic radiological procedures are also very high (the dose of a multi-slice cardiac CT scan is equal to the dose from 300 chest X-rays) and are of great concern as well; thus such patients would also benefit from the affordable and effective radioprotectors. There is also importance for public safety to have radioprotective agents readily available in the event of a nuclear accident or terrorist attack.
Radioprotective agents that could be given prior to, or even during, radiation exposure would be of significant value in alleviating the side effects associated with exposure to ionizing radiation. Currently there are no FDA-approved radioprotectors. It would be extremely beneficial for hundreds of millions of people to have access to food supplements that could fill the niche in the absence of radioprotective drugs.
Fungal melanins can function as energy transducing molecules capable of capturing high energy electromagnetic radiation and converting it into an energy form that is useful to fungal cells (1). Furthermore, fungal melanins can be effective shields against radiation; the efficacy of radioprotection by melanins is dependent on their chemical composition and spatial arrangement (2). In addition to free reactive radical scavenging, radioprotection by melanins involves prevention of free radical generation by Compton recoil electrons through gradual recoil electron energy dissipation by the n-electron-rich melanin until the kinetic energy of recoil electrons becomes low enough to be trapped by stable free radicals present in the pigment (3). It has also been shown that melanin-based nanoparticles protect bone marrow in mice subjected to external whole body radiation or radioimmunotherapy (4).
The present invention addresses the need for radioprotectants in humans at risk for radiation exposure using melanin-based products.